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TAVI noninferior to surgery for elderly, severe AS patients at moderate operative risk: UK TAVI
Study finds TAVI noninferior to SAVR for all-cause mortality at 1-year in patients with severe, symptomatic AS over 70 years at moderately increased surgical risk
Transcatheter aortic valve implantation (TAVI) was noninferior to surgery, a United Kingdom (UK) study found recently, for elderly patients with severe, symptomatic aortic stenosis (AS) at moderately increased operative risk.
The randomized clinical trial titled UK TAVI – published in the Journal of American Medical Association (JAMA) on May 17 by investigators – found 1-year all-cause mortality rates with TAVI were comparable to surgical aortic valve replacement (SAVR).
TAVI – an alternative treatment to surgery with SAVR also known as transcatheter aortic valve replacement (TAVR) – is approved for symptomatic AS patients at high operative risk.
The relatively minimally invasive stenting procedure also started gaining approval for AS patients at lower operative risk, although the benefits of TAVI in such groups are largely uncertain.
UK TAVI was conducted at 34 centers in the UK and enrolled 913 patients with severe, symptomatic AS over 70 years of age at moderately increased operative risk (median age: 81 years; 46% female; median STS mortality risk score: 2.6%) to determine whether TAVI outcomes were comparable to SAVRs.
458 patients were randomized to a TAVI treatment group that allowed any approved valve in the UK along with all access routes and 455 patients were randomized to SAVR.
Analysis showed the balloon-expandable SAPIEN 3 valve (Edwards Lifesciences; California; US) accounted for most operations (57%), followed by the self-expanding Evolut R valve (Medtronic; Minnesota, US) at 16%. Transfemoral access was most common for the TAVI arm (96%). Nearly all SAVR patients received a xenograft bioprosthesis.
It is reassuring that UK TAVI – conducted with multiple valve types – confirmed major findings from previous RCTs that were limited to specific TAVI valves.
Follow-up continued to April 2019 for the primary endpoint of all-cause mortality and 36 secondary outcomes at 1-year. The noninferiority margin was prespecified to 5% (upper limit of 1-sided 97.5% CI).
At 1 year, results showed noninferiority for all-cause mortality between TAVI and SAVR (21 vs. 30 deaths; 4.6% vs. 6.6%; adjusted AR difference -2.0%, 1-sided 97.5% CI, −∞ to 1.2%; P<0.01 for noninferiority).
Analysis of secondary endpoints showed no major differences except the TAVI arm had a shorter mean duration of post-procedural hospitalization (TAVI vs. SAVR: 3 vs 8 days) and fewer major bleeding events (7.2% vs 20.2%; aHR 0.33, 95% CI, 0.24-0.45).
However, TAVI showed higher rates of vascular complications (10.3% vs 2.4%; aHR 4.42, 2.54-7.71); conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; aHR 2.05, 1.43- 2.94); and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (AR vs no AR: aOR 4.89, 3.08-7.75).
“Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery for all-cause mortality at 1 year,” the investigators wrote.
Findings back expanding TAVI indications; more needed on long-term durability for young AS
On findings, experts applauded the trial design that allowed for wide application of findings in a clinical setting where ambiguity reigned for AS patients at moderately increased risk.
“UK TAVI enrolled all patients who met eligibility criteria, [and] simply put, included all symptomatic patients older than 80 years of age with severe AS and those older than 70 with increased operative risk,” Catherine M. Otto, MD, PhD (University of Washington School of Medicine, Seattle, USA) and Jae-Kwan Song, MD (Asan Medical Center, Seoul, South Korea) wrote in a related New England Journal of Medicine(NEJM) editorial.
“When compared to [the PARTNER 3 or Evolut Low Risk] trials in the US, patients in UK TAVI had a significantly higher mean age (81 vs. 75 years) and predicted mortality according to the Society of Thoracic Surgery (STS) score (2.6% vs. 1.9%) or European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (2.0% vs. 1.5%).”
The authors noted that the investigator-initiated design took a step forward from previous sponsor-initiated studies by including various valve types, “further supporting current guideline recommendations for TAVI in older adults with severe AS symptoms.”
Although international guidelines strongly favor SAVR for most patients with severe AS, the latest 2020 American guideline recommended both TAVI and SAVR for symptomatic patients between 65 and 80 years (Class I) and younger patients with a life expectancy of fewer than 10 years (Class Ia).
The 2021 European guidelines also recommended TAVI for patients over 75 years of age at high surgical risk (Class I).
Otto and Song further urged longer follow-up studies to confidently transition younger AS patients from SAVR to TAVR, primarily for the “unsolved problem” of calcification and degeneration of bioprosthetic valves.
“Experience shows that most patients with surgical bioprosthetic valves had normal valve function until approximately 10 years after implantation, which was followed by substantially increased risks of valve deterioration and hemodynamic failure. TAVI bioprostheses will also likely be affected by leaflet calcification and valve degeneration, although the time course is uncertain.”
“We need longer-term data but this has been a challenge because most patients undergoing TAVI – as in the current study – are typically older than 70 years and even aged 80 years, which means limited follow-up and a marked survival bias, limiting extrapolation of outcome data to younger patients.”
While awaiting the outcomes of SAVR and TAVI for the wide spectrum of AS patients, primary and secondary prevention with lifestyle and medical therapy were stressed as key treatment strategies.
“The best valve for each patient is their own, and the goal should be to ensure that their own valve functions normally. While awaiting the development of effective therapies for calcific AS, clinicians need to focus on primary and secondary lifestyle and medical therapies to prevent the initiation or progression of calcific aortic stenosis, rather than just treating obstruction due to end-stage disease.”
The UK TAVI Trial Investigators. “Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients with Aortic Stenosis.” JAMA, vol. 327, no. 19, 2022, p. 1875., doi:10.1001/jama.2022.5776.
Otto, Catherine M., and Jae-Kwan Song. “Treatment of Aortic Stenosis with Transcatheter Aortic Valve Implantation.” JAMA, vol. 327, no. 19, 2022, p. 1870., doi:10.1001/jama.2022.5424.